{"doi":"10.17615/r9yf-6n86","title":"Toll-like receptor 4 mediates intrauterine growth restriction after systemic Campylobacter rectus infection in mice: TLR4 mediates IUGR after C. rectus infection","abstract":"Campylobacter rectus is associated with fetal exposure and low-birth weight in humans. C. rectus also invades placental tissues and induces fetal intrauterine growth-restriction (IUGR) in mice, along with Toll-like receptors (TLR4) overexpression, suggesting that TLR4 may mediate placental immunity and IUGR in mice. To test this hypothesis we examined the effect of in vitroTLR4 neutralization in trophoblastic proinflammatory activity and studied the IUGR phenotype in a congenic TLR4-mutant mouse strain after in vivo C. rectus infection. Human trophoblasts were pretreated with TLR4 neutralizing antibodies and infected with C. rectus; pro-inflammatory cytokine production was assessed by cytokine multiplexing assays. Neutralizing TLR4 antibodies significantly impaired the production of pro-inflammatory cytokines in trophoblastic cells after infection in a dose-dependent manner. We used a subcutaneous chamber model to provide a C. rectus challenge in BALB/cAnPt (TLR4Lps-d) and wild-type(WT) females. Females were mated with WT or TLR4Lps-dmales once/week; pregnant mice were infected at (E)7.5 and sacrificed at (E)16.5 to establish IUGR phenotypes. Maternal C. rectus infection significantly decreased fetal weight/length in infected WT when compared to sham WT controls(PLps-d−/− mice did not show statistically significant differences in fetal weight and length when compared to WT controls(P>0.05). Furthermore, heterozygous TLR4Lps-d −/+fetuses showed IUGR phenotype rescue. We concluded that TLR4 is an important mediator of trophoblastic proinflammatory responses and TLR4-deficient fetuses do not develop IUGR phenotypes after C. rectus infection, suggesting that placental cytokine activation is likely to be mediated by TLR4 during low birth weight/preterm delivery pathogenesis.","journal":"UNC Libraries","year":2020,"id":135633,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9561,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":540004,"name":"K.M. Caron","orcid":null,"position":1,"is_corresponding":false},{"id":593751,"name":"S.P. Barros","orcid":null,"position":2,"is_corresponding":false},{"id":526072,"name":"S. Offenbacher","orcid":null,"position":3,"is_corresponding":false},{"id":593750,"name":"R.M. Arce","orcid":null,"position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T23:16:35.237665Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}